Conclusions Mnemonic and executive deficits do no appear to be
epiphenomena of depressive disorder. A focus on the interactions between
motivation, affect and cognitive function may allow greater understanding of
the interplay between key aspects of the dorsal and ventral aspects of the
prefrontal cortex in depression.

There has been a renewal of interest in testing patients with depression on
a broad range of neuropsychological tasks in the last decade. It has promoted
a growing awareness that, like schizophrenia and neurological disorders, mood
disorders may be associated with a distinct pattern of cognitive impairment.
Such impairments of cognitive function are seldom measured. This is surprising
because it is easier objectively to measure memory impairment, for example,
than it is to characterise other core features of depression such as the
severity of depressed mood or sleep disturbance. Cognitive impairment is also
likely to be a key factor affecting the subject's ability to function
occupationally and, hence, the timing of his or her return to work. However,
also central to current interest is the effort to link theories of cognitive
neuropsychology to the anatomy and physiology of brain function. If depression
is indeed a brain disease then neuropsychological impairments may lead us to
the relevant neural substrate(s). In this article we aim to review the
cognitive deficits reported in depression and how these deficits may reflect
disruption in the anatomy and function of putative frontosubcortical neuronal
pathways.

METHOD

Computerised Medline and Psycinfo searches were performed from January 1966
to September 1999 using the terms NEUROPSYCHOLOGICAL TESTING, COGNITIVE
FUNCTION, DEPRESSION and DEPRESSIVE DISORDERS. Where a large number of studies
had been performed, only the most methodologically rigorous are highlighted.
Where there is a paucity of studies (e.g. of follow-up), those available are
overviewed. This is not an all-inclusive review, and the choice of articles
reflects the authors' qualitative assessment of current themes of importance
in this area of research.

RESULTS

Cognitive deficits in depression

It is now commonly accepted that depression is associated with a number of
deficits in episodic memory and learning (see
Goodwin, 1997 for a review).
This finding is consistent across most studies and appears to involve both
explicit verbal and visual memory in patients with both melancholic
(endogenous) and non-melancholic (non-endogenous) depression
(Austin et al, 1999).
Implicit memory taks, on the other hand, appear to be spared
(Hertel & Hardin, 1990;
Denny & Hunt, 1992;
Bazin et al, 1994;
Danion et al, 1995;
Ilsley et al, 1995).
Temporal lobe lesions typically disrupt episodic memory; given that reductions
in hippocampal volume are demonstrated in patients with major depression
(Sheline et al, 1996)
it may be that impaired mnemonic function is associated with dysfunction of
the hippocampus in depression.

The initial studies examining impairment in executive tasks produced
conflicting results, although, in general, significant impairment was seen in
subjects with more severe depression
(Friedman, 1964;
Raskin et al, 1982;
Silberman et al,
1983). The pattern of executive deficits described in recent
reports has been relatively consistent across studies (Austin et al,
1992a,
1999;
Beats et al, 1996;
Purcell et al, 1997;
Murphy et al, 1999),
with a single exception (Elliott et
al, 1996). Thus, Beats et al
(1996), examining a more
severely depressed elderly sample found these subjects to be most prominently
impaired on verbal fluency and attentional set-shifting. Purcell et
al (1997) in a study of
younger out-patients with moderate depression reported no impairment on
working memory, but did find impairment on measures of motor speed and
attentional set-shifting, with half of the depression group failing to
complete all stages of this task. The number of trials to reach criterion on
the extra-dimensional component of the task (which may indicate
perseveration), was similar to that seen in the elderly subjects with
depression in the Beats et al
(1996) study. These ‘
impaired’ subjects had a higher rate of admissions for treatment
of depression, suggesting that those with overall greater illness severity are
more impaired on set-shifting tasks. However, the studies by Channon
(1996) and Channon & Green
(1999) would suggest that
impairment in executive function is also present in younger (mean 20-40 years)
patients with dysphoria, and those with less severe depression (mean Beck
Depression Inventory (Beck,
1963) scores of 17-21).

Austin et al
(1992a,
1999) examined two separate
depression samples, both of which were divided into endogenous and
non-endogenous subsets using narrow definitions of endogenous depression —
namely the Newcastle system
(Carney et al, 1965),
with the Austin et al
(1999) study further
subdividing the samples into melancholic and non-melancholic according to the
CORE instrument (Parker et al,
1994). Both studies revealed selective executive deficits in
subjects with melancholic (endogenous) compared with non-melancholic
(non-endogenous) depression. In the Austin et al
(1999) study subjects with
endogenous/melancholic depression were impaired (as in the
Austin et al,
1992a study) on working memory (digits backwards) as well
as on tasks heavily reliant on set-shifting (Trails B, and digit symbol
substitution); in addition there was an increased perseverative response on
the Wisconsin Card Sorting Task (WCST;
Heaton, 1981), while tasks of
inhibitory control (Stroop test (Golden,
1987), WCST set initiation and maintenance) and conceptual tasks
(similarities, verbal fluency), were spared. Finally, Murphy et al
(1999), in a study comparing
the performance of subjects with depression and mania on a novel affective
set-shifting task, reported that subjects with depression were impaired in
their ability to shift the focus of attention (apparently corresponding to the
set-shifting component of the WCST), while patients with mania were impaired
in their ability to inhibit behavioural responses (apparently corresponding to
the interference effect of the Stroop test). This latter study further
confirms the earlier trend reported for selective set-shifting deficits in
depression. The exception to this finding was the study by Elliott et
al (1996) of middle-aged
subjects with moderate, predominantly chronic depression, who demonstrated
impaired ability on the Tower of London, verbal fluency and spatial working
memory tasks, but intact performance on a modified and easier version of the
Cambridge Neuropsychological Battery (CANTAB) set-shifting task
(Robbins et al,
1994). It may be that this version of the task was at ceiling and
unable to detect an impairment in set-shifting.

Severity of depression, depressive subtype and impact upon cognitive
performance

The finding that subjects with depression were impaired on verbal recall
while performing normally on verbal recognition
(Roy-Byrne et al,
1986) led Weingartner to suggest that patients with depression
generally had difficulty with ‘effortful’ as compared to ‘
automatic’ tasks (Weingartner
et al, 1981; Cohen
et al, 1982;
Roy-Byrne et al,
1986). Based on correlation findings alone, the authors
hypothesised that both the motor and cognitive impairments seen in depression
could be secondary to an underlying motivational deficit, rather than arising
in their own right. Similarly, Bazin et al
(1994) proposed that the
dissociation between explicit (impaired) and implicit (intact) memory tasks
seen in patients with depression (Hertel & Hardin, 1990; Denny & Hunt, 1992; Bazin et
al, 1994; Danion et
al, 1995; Ilsley et
al, 1995) was also a result of the greater effort required
for the former and the more automatic performance of the latter. The ‘
effortful-automatic’ hypothesis has been undermined by a number
of studies. Frith et al
(1983), Wolfe et al
(1987), Golinkoff &
Sweeney (1989), Austin et
al (1992a,
1999) and Brown et al
(1994) have all reported both
impaired verbal recall (an effortful task) and recognition (an automatic task)
in subjects with depression. In the CANTAB's Delayed Match to Sample Task
(DMST), the mnemonic encoding deficit cannot be dependent upon effortful
processing alone because subjects with depression showed deficits at zero
delay as well as later times (Abas et
al, 1990; Moffoot et
al, 1994).

The impact of depressive subtype on task performance has been explored in a
small number of studies. Byrne
(1977) and Cornell et
al (1984), both using the
Newcastle scale to define subjects with endogenous and non-endogenous
depression, found impairment of complex reaction time in subjects with
endogenous depression alone. Fromm & Schopflocher
(1984), also using the
Newcastle criteria, and Rush et al
(1983) using the Research
Diagnostic Criteria criteria reported that subjects with endogenous depression
were more impaired on all cognitive tasks (Trails, Stroop test, visual recall
and complex attention) than subjects with non-endogenous depression. The
relationship between severity and depression subtype is a further confounder.
Thus, while Austin et al
(1992a,
1999) reported frontal deficits
only in their subjects with narrowly defined (Newcastle and CORE) endogenous
or melancholic depression, these disappeared after covarying for Hamilton
scores (Austin et al,
1999), indicating that this pattern of frontal deficits was more
likely to be present as a result of depression severity rather than depressive
subtype. A useful probe of the effects of severity per se is provided
by the significant diurnal variation in mood seen in many subjects with
melancholia, where depressed mood is typically worse early in the day. It has
been demonstrated that these subjects perform less well on most cognitive
tasks (except for the DMST) in the morning compared to evening, with the
opposite finding in controls (Moffoot
et al, 1994). In summary, melancholic subtype and
depression severity both appear to contribute to the neuropsychological
deficits seen in subjects with depression. Some tests are highly dependent on
current mood severity, others are not: differential effects of this sort may
offer clues to the mechanisms and brain networks involved.

The neuropsychological deficits that are correlated with depression
severity have attracted controversy. A number of researchers have applied the
cognitive-behavioural paradigms of motivation, ‘response bias’ and ‘
negative cognitive set’, to explain the neurocognitive
impairments seen in depression. Motivation has been defined as “the
ability to initiate appropriate activity either spontaneously or in response
to environmental cues” (Lezak,
1995). Since the implied stimulus—reward associations are
partly predicated upon the ability to experience pleasure, motivation must
also in some way be closely linked to hedonic drive and, in turn, to affect.
It is difficult to imagine one without the other. Our understanding of
motivation is based predominantly on the study of patients with frontal lobe
lesions, in whom both motivation and affect are significantly compromised,
suggesting, at least in those patients, “that affect and drive (i.e.
motivation) are two sides of the same coin”
(Lezak, 1995). It is not
clear, therefore, that to study reduced motivation is not in some sense to
study depression.

A number of studies have proposed that impaired motivation in depressed
patients can be measured as lack of an appropriate response to explicit reward
(Miller & Lewis, 1977;
Layne, 1980;
Henriques et al,
1994), where depressed patients may not perceive reward as
reinforcing because of a low hedonic capacity
(Meehl, 1975;
Hughes et al, 1985).
This lack of response to reward may manifest as a response bias. Conservative
response bias, or the tendency for patients with depression to require a
greater degree of certainty (or reward) before they respond, has been put
forward as a cause of impaired performance by some
(Miller & Lewis, 1977);
Henriques et al,
1994), but not all (Deptula
et al, 1991; Channon
et al, 1993) authors. Henriques et al
(1994) in a controlled study
of subjects with ‘dysphoria’ (defined by their score on the Beck
Depression Inventory), found a lack of improvement in task performance in
response to financial incentive, while response to neutral and punishment
conditions was the same in both groups — implying that subjects with
dysphoria were selectively less responsive to reward mechanisms than controls.
This lack of response to financial incentive was also reported by Richards & Ruff (1989) in their
sample of out-patients with depression. These studies did not establish how
tasks varied in their sensitivity to motivation: indeed, they assumed that
finding the effect for one task meant it could be generalised to all
tasks.

Elliott et al
(1997) suggested that response
bias to negative feedback within the testing paradigm was associated with
impaired cognitive performance in subjects with depression compared with
controls. Their findings suggested that a subject's awareness of failure on
one problem dramatically increased the chance of failure on the subsequent
problem. The authors proposed two possible explanations: either subjects with
depression demonstrate a lack of adequate response to negative feedback (with
inability to expend greater effort on a subsequent task); or they have a
stronger negative reaction to negative feedback — manifesting
cognitively as a ‘negative cognitive set’
(Beck, 1963) — and
perform more poorly as a result. Given that the authors submitted their
data-set to many post hoc statistical tests, the findings were by
nature, exploratory. Indeed, other studies
(Purcell et al, 1997;
Shah et al, 1999)
using a similar paradigm in subjects with equally severe depression have not
reported similar results.

Negative cognitive set (Beck,
1963) was not explicitly measured by Elliott et al
(1997), but its effect upon
cognitive performance has also been explored using tasks that test memory for
negatively valenced words. Many studies have demonstrated that such words are
selectively recalled over positively or neutrally valenced words, implying
that the subject with depression has increased access to them
(Matt et al,
1992).

Clearly, a motivation deficit has the potential to impair the performance
of all neurocognitive tasks. That it fails to do this invites the proposition
that some tasks are more sensitive to such effects than others. This section
has highlighted the need to clarify the concepts before the interaction
between motivation, depressed affect and cognitive function can be
understood.

Recovery from depression: is there persistent neuropsychological
impairment?

A small number of studies have compared the performance of subjects who
have recovered from depression with that of matched controls. Using this
design, Paradiso et al
(1997) found significant
neurocognitive impairment in subjects who had recovered from unipolar
depression which was most marked on set-shifting tasks and not related to
medication status. Marcos et al
(1994) in a study of subjects
with DSM—III—R (American
Psychiatric Association, 1987) melancholia who had recovered for 3
months or more, reported persistent deficits in both immediate memory and
delayed recall of visual and verbal material, and block design.

Testing before and after recovery is a potentially powerful method of
identifying and distinguishing state- from trait-related cognitive deficits,
but the prospective studies done to date also have methodological limitations.
In particular they frequently use inadequate definitions of recovery
(Sternberg & Jarvik, 1976;
Jones et al, 1988;
Peselow et al, 1991;
Bazin et al, 1994;
Moreaud et al, 1996),
do not control for the potential effects of medication and electroconvulsive
therapy and fail to show that task performance is within the normative range
at recovery (Tarbuck & Paykel,
1995). Abas et al
(1990) tested elderly patients
with endogenous depression on a number of memory measures and reported that
half of those performing poorly at baseline were still impaired at recovery in
spite of improved Mini-Mental State Examination (MMSE;
Folstein et al, 1975)
scores and a lack of clinical evidence for incipient dementia and independent
of medication status. In a similar sample of elderly patients, Beats et
al (1996) also found that
many, but not all deficits had remitted upon recovery: specifically, measures
of simple and choice reaction times, perseveration on the setshifting task and
verbal fluency did not fully recover. Peselow et al
(1991) in a study of patients
with unipolar depression treated with imipramine for 4 weeks, reported
significant improvement in all mnemonic measures in treatment responders only.
They concluded that, in memory tasks at least, recovery of mood was associated
with significant cognitive improvement. This finding echoed the earlier
findings of a small study by Calev et al
(1986) and that of Bazin
et al (1994) neither
of which found residual impairment in either explicit (verbal and visual) or
implicit memory tasks upon recovery. In contrast, Sternberg & Jarvik
(1976) reported that in
endogenous subjects responding to a tricyclic antidepressant after 4 weeks,
improvement in immediate memory was related to degree of depressive recovery,
while performance on learning and short-term memory tasks remained impaired.
Trichard et al (1995)
in a controlled study of executive task performance in middle-aged subjects
with severe depression, reported improved performance on the verbal fluency
task but not the Stroop task upon recovery. Thus, at present a residual
deficit in mnemonic and executive function appears to be seen in some patients
with a history of depression. Its rela-tionship to crucial epidemiological
variables such as age, treatment, duration and chronicity of illness and
number of episodes (Kessing,
1998), remains to be more clearly determined.

Relationship between age, microvascular disease and cognitive
impairment in depression

Age is associated with a progressive decline in cognitive function. In
particular, mental processing becomes slowed; there is poorer performance on
effortful tasks; and mental inflexibility, susceptibility to distractors and
perseveration become more prominent. These are the very tasks in which
subjects with depression, and especially those with severe depression
(endogenous or melancholic), are impaired, and thus age per se is a
significant confounder for cognitive impairment in depression
(Jorm, 1986).

Advancing age is also associated with an increase in microvascular brain
disease, which appears to be particularly marked in subjects with late-onset
depression (Brown et al,
1992). Current aetiological models of late-life depression have
focused particularly on the presence of microvascular disease in deep white
matter suggested by magnetic resonance imaging studies (see
Hickie & Scott, 1998 for a
review). Severe cognitive impairment is also frequently found in older
patients with severe depression and, in a significant proportion, appears not
to be fully reversible (Abas et
al, 1990; Alexopoulos
et al, 1993; Hickie
et al, 1997). Many older patients have concurrent
hypertension, cardiovascular and cerebrovascular disease, and longitudinal
studies suggest that patients with depression with these medical risk factors
may be at increased risk of cognitive impairment and/or dementia
(Hickie & Scott, 1998 for
review). Thus, some older patients with persistent cognitive deficits due to
treatment-resistant depression may have a comorbid incipient vascular
dementia.

A number of studies have examined the relationship between magnetic
resonance imaging and cognitive task performance in older subjects with
depression, and all report a significant correlation between the presence of
deep white matter hyperintensities in subjects with late-onset depression and
poorer cognitive task performance, in particular on executive and psychomotor
tasks (Hickie et al,
1995; Lesser et al,
1996; Kramer-Ginsberg et
al, 1999). Although microvascular pathology, which in some
cases is associated with vascular dementia, may account for the persistent
cognitive deficits seen in older subjects with late-onset depression, such
processes currently seem unlikely to contribute to the persistent cognitive
deficits reported in many younger (i.e. under 60 years old) subjects with
depression. However, we do not yet understand the neurobiological consequences
of severe depression. It remains possible that there are vascular sequelae
that we can only see with available technology when expressed in the ageing
brain. Alternatively there may be vascular factors that predispose to
depression in severe early-onset cases or may even mediate the effects of
precipitating life events.

DISCUSSION

Methodological limitations of cognitive testing in depression

There are a number of significant limitations associated with the use and
interpretation of standard neurocognitive testing in psychiatric disorders
such as depression. While it is easy to equate a deficient neurocognitive
function with the location of a neuroanatomical defect,

“many putatively ‘localising’ neuropsychological
procedures were derived from studies of patients with focal lesions... they
reflect a view of brain—behaviour relationships based upon vascular
anatomy... whether this understanding of cerebral localisation applies to less
focal diseases remains to be determined”
(Caine, 1986).

Most cognitive tasks tap a number of cognitive domains, making it difficult
to tease out the primary functional deficit associated with impairment on any
one task. The WCST, which has been the classic tool to detect a frontal
lesion, exemplifies a number of these issues. In particular, it relies on
examiner feedback for its performance and assesses several key cognitive
domains: shifting the sorting rule when negative feedback to a previous
positive stimulus—reward association occurs; memorising previous rules
to ensure efficient rule testing; and establishing or rejecting rules by
deductive reasoning (Dehaene &
Changeux, 1991). The use of properly constructed test batteries
assessing a broad range of functions in order to allow for assessment of
patterns of impairment may go some way to circumventing this problem but it is
unlikely to solve it (Keefe,
1995). This is particularly the case for executive function, where
the nature of the neuropsychological construct itself remains controversial.
Indeed there is strong evidence that the general factor, or Spearman's
g, which identifies covariation between performance on many tests,
may be the critical measure of frontal lobe function
(Duncan et al,
1995).

Finally, while most neurocognitive tasks are designed to eliminate or
minimise the effects of reward and reinforcement, it is not possible to do
this for executive tasks that are dependent on feedback for their performance.
The structured nature of testing may mask deficits in motivation,
self-monitoring and planning which often contribute to the clinical
presentation associated with depression.

Neurocognitive ‘double dissociations’ and the putative
pathogenesis of depression

The gold standard in any attempt at localisation of neuropathophysiology by
means of neurocognitive testing is the identification of mutually exclusive
profiles of cognitive impairment or ‘double dissociations’, which
are in turn linked with focal anatomical lesions
(Gazzaniga et al,
1998). The double dissociation method has been a powerful tool in
identifying different domains of prefrontal function in animal lesion studies
(Dias et al, 1996;
Rolls, 1996). In humans, this
method is most applicable to the study of subjects with either focal brain
lesions or relatively focal neuropathology such as Parkinson's disease or
Huntington's chorea. In complex disorders such as depression, the assumption
that impaired neurocognitive function will reveal the nature of the neural
defect underlying the disorder remains speculative.

While double dissociations are more difficult to demonstrate in subjects
with functional psychiatric disorders, there is an emerging body of work which
suggests that this may be feasible. Austin et al
(1999), using a battery with a
large number of frontal tasks, demonstrated a dissociation between two sets of
key frontal domains: set-shifting and working memory on the one hand, and
inhibitory control on the other. Human lesion
(Grattan et al, 1994)
and imaging (Courtney et al,
1997) work has suggested an association between the dorsolateral
prefrontal cortex and frontal cognitive deficits in depression, with a
relative sparing of lateral orbitofrontal and anterior cingulate regions which
have been associated with inhibitory control as reflected by performance on
the Stroop task (Pardo et al,
1990; Bench et al,
1993). Such hypotheses require specific testing in activation
studies with functional imaging.

Integrating the neurocognitive and affective manifestations of
depression into a functional neuroanatomical framework

There is now significant evidence, both from animal and human studies,
suggesting the existence of distinct, parallel functional networks or loops
linking prefrontal and subcortical regions (Alexander et al,
1986,
1990;
Cummings, 1993). Disruption in
several of these functional networks has now been implicated in the
pathogenesis of a number of psychiatric disorders including major depression
(Austin & Mitchell,
1995).

It was originally hypothesised
(Cummings, 1993) that patients
with depression have impaired function in the limbic loop with effects upon
the affective, autonomic and vegetative domains. This has been partially
supported by a number of imaging studies suggesting that some regions
functionally linked to the anterior cingulate (part of the limbic loop), and
the subgenual prefrontal cortex (PFC), are key functional regions modulating
affect in depression (Austin et
al, 1992b;
Drevets et al, 1997;
Mayberg et al, 1997).
Drevets et al (1997)
demonstrated significant reduction in both perfusion and, more intriguingly,
brain volume in the subgenual region in patients with unipolar and bipolar
depression. Finally, Goodwin et al
(1993) and Mayberg et
al (1997) both
demonstrated normalisation of perfusion in the anterior cingulate upon
recovery.

Findings from activation studies in normal control subjects and subjects
with depression are strongly suggestive of a close integration between the
dorsolateral prefrontal cortex (DLPFC) (implicated in the set-shifting
deficits of depression described above) and the subgenual cingulate in
depression. Thus, Teasdale et al
(1999) reported in normal
subjects that certain components of the medial prefrontal cortex (including
the anterior cingulate) appear to be involved in the cognitive induction of a
negative affect, thereby implying close integration between the dorsolateral
and limbic circuits. Mayberg et al
(1999) examined the impact of
negative mood induction, both in normal control subjects and those subjects
who had recovered from depression, on cerebral perfusion. Induced sadness was
associated with an increase in subgenual cingulate cerebral blood flow and a
decrease in DLPFC, while recovery from depression was associated with the
reverse pattern. Intriguingly, an earlier lesion study by Bechara et
al (1996) demonstrated
that patients with ventromedial lesions had relatively preserved cognitive
function, except for decision-making, which was impaired when this relied upon
the ability to attach emotional salience to the task situation. Their
findings, like those of Teasdale et al
(1999) and Mayberg et
al (1999), suggest that
affect and cognitive function may be anatomically linked at the level of the
ventromedial or orbitofrontal regions. Exactly how this maps onto the
reciprocal interaction between two key prefrontal regions (dorsolateral and
orbitofrontal) and their frontal subcortical connections remains a challenge.
Nevertheless, in light of these findings, the initial proposal that the
frontosubcortical networks (Alexander et al,
1986,
1990) essentially operate
independently needs to be revised.

Are these neuropsychological deficits simply epiphenomena of
depression?

The commonly held view that neuropsychological deficits in depression are
simply epiphenomena of age, poor motivation, inattention or response bias now
appears somewhat dated. Correlational studies evaluating the impact of age,
task difficulty and depression severity upon task performance in depression
partially favour the effortful—automatic hypothesis. What such a finding
may mean remains uncertain. One view is simply an extension of the
epiphenomena perspective: if patients feel unwell they will not try so hard.
However, this fails to acknowledge that the subjective basis of all
experience, including action, is neuronal. An increased sense of effort will
have a neurobiology. A possible explanation for this is that failure of
executive function in depression may be closely related to an increased sense
of subjective effort that involves the prefrontal cortex.

A small number of studies indicate persistent cognitive impairment upon
recovery in mood disorder, as noted above. These findings are reported in all
age groups, although more frequently in older subjects. Thus, while
psychosocial explanations of mood disorder are often uncritically accepted,
the presence of neuropsychological deficits is important evidence that
enduring brain abnormalities are implicated in the aetiology of depressive
disorder. If cognitive impairment were simply secondary to the severity of
depressed mood, then it would be expected to fully recover upon remission of
the episode, and certainly would not be expected to appear in young subjects
with dysphoria (mild depression).

Do these cognitive deficits help us identify the functional
neuropathology of depressive disorders?

If cognitive deficits are intrinsic expressions of the brain changes in
depressive illness, and we believe they are, can they help us identify the
functional neuropathology of depressive disorders? The consistent impairments
of memory function, which are not dependent on the acute mood changes
associated with diurnal mood variation when tested using almost purely
mnemonic tests (Moffoot et al,
1994), suggest that as we learn more about memory mechanisms in
humans we shall learn more about depression. Selective set-shifting deficits —
both on cognitive and affective set-shifting tasks — are also
assuming an increasing interest in depression. Restricted lesions of the
ventromedial prefrontal cortex have profound effects upon executive function,
the recognition of emotion in others and, probably, upon the experience of
mood (Damasio, 1994;
Rolls et al, 1994;
Hornak et al, 1996).
The apparent localisation to quite a small brain area of a critical link
between affect and cognition comes as something of a surprise, but it is
supported by a number of functional imaging studies and by some recent
neuropsychological studies in depression
(Murphy et al, 1999;
Austin et al,
1999).

Clinical Implications and Limitations

CLINICAL IMPLICATIONS

Mood lowering and cognitive impairment deserve to be considered as
comparably important manifestations of depressive disorder.

Formal cognitive testing could be a useful adjunct in the clinical
evaluation of patients with depression, both at index episode, but more
particularly upon recovery.

Where microvascular disease or incipient dementia may account for the
cognitive deficits seen in late-onset depression, magnetic resonance imaging
could be a useful tool in diagnostic clarification.

LIMITATIONS

Cognitive activation imaging studies in depression are not covered in this
review.

The article is selective in its focus and does not provide an exhaustive
review of all cognitive studies in depression.

The specificity of cognitive deficits seen in depression is not discussed
in this review, that is, a comparison between depression and other psychiatric
disorders is not drawn.

Acknowledgments

We are most grateful to Professor Perminder Sachdev for his excellent
comments on an earlier manuscript and to Professor Gordon Parker for his
editorial overview.